methyl 3-(4-chlorophenyl)-1-methyl-1H-pyrazole-5-carboxylate | 1391108-14-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: methyl 3-(4-chlorophenyl)-1-methyl-1H-pyrazole-5-carboxylate
• 英文别名: methyl 5-(4-chlorophenyl)-2-methylpyrazole-3-carboxylate
• CAS: 1391108-14-7
• 化学式: C₁₂H₁₁ClN₂O₂
• mdl: MFCD22573451
• 分子量: 250.685
• InChiKey: DRCATWBDNFNOEG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  44.1
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  methyl 3-(4-chlorophenyl)-1-methyl-1H-pyrazole-5-carboxylate 在 吡啶 、 N-碘代丁二酰亚胺 、 四(三苯基膦)钯 、 ammonium cerium (IV) nitrate 、 palladium 10% on activated carbon 、 水 、 氢气 、 potassium carbonate 、 N,N-二异丙基乙胺 作用下， 以 甲醇 、 乙二醇二甲醚 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 90.0 ℃ 、101.33 kPa 条件下， 反应 2.75h， 生成 (R)-3-(4-chlorophenyl)-4-(3-(4-(4-(4-((4-(dimethylamino)-1-(phenylthio)butan-2-yl)amino)-3-nitrophenylsulfonamido)phenyl)piperazin-1-yl)phenyl)-1-methyl-1H-pyrazole-5-carboxylic acid
  参考文献：
  名称：

  A Potent and Highly Efficacious Bcl-2/Bcl-xL Inhibitor

  摘要：

  Our previously reported Bcl-2/Bcl-xL inhibitor, 4, effectively inhibited tumor growth but failed to achieve complete regression in vivo. We have now performed extensive modifications on its pyrrole core structure, which has culminated in the discovery of 32 (BM-1074). Compound 32 binds to Bcl-2 and Bcl-xL proteins with K-i values of <1 nM and inhibits cancer cell growth with IC50 values of 1-2 nM in four small-cell lung cancer cell lines sensitive to potent and specific Bcl-2/Bcl-xL inhibitors. Compound 32 is capable of achieving rapid, complete, and durable tumor regression in vivo at a well-tolerated dose schedule. Compound 32 is the most potent and efficacious Bcl-2/Bcl-xL inhibitor reported to date.

  DOI：

  10.1021/jm4001105
• 作为产物：
  描述：

  甲基 4-(4-氯苯基)-2,4-二羰基丁酸 在 potassium carbonate 、 一水合肼 、 溶剂黄146 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 methyl 3-(4-chlorophenyl)-1-methyl-1H-pyrazole-5-carboxylate
  参考文献：
  名称：

  Pyrazole derivatives as inhibitors of arachidonic acid-induced platelet aggregation

  摘要：

  Antiplatelet drugs are promising therapeutics to intervene with platelet aggregation in arterial thrombosis, most prominently in myocardial infarction and ischemic stroke. Here, we describe the synthesis and structure activity relationships of potent inhibitors of platelet aggregation based on the 1,5-diarylpyrazol-3-carboxamide scaffold. Analogs from this series demonstrated potent anti-aggregatmy activities against arachidonic acid-induced platelet aggregation, as measured by turbidimetric method of Born. 1,5-Diarylpyrazole-3-carboxamides obtained with small-basic amines (7, 8, 50, 51, 61, 62) displayed the strongest activity with IC50 values in low nanomolar range (5.7-83 nM). On the basis of their high potency in cellular environment, these straightforward pyrazole derivatives may possess potential in the design of more potent compounds for intervention with cardiovascular diseases. (C) 2013 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2013.03.048

文献信息

• 3-Aryl-5-pyrazole-carboxylic-acid derivatives, their preparation and pharmaceutical compositions
  申请人：ELI LILLY AND COMPANY

  公开号：EP0112623A2

  公开（公告）日：1984-07-04

  Pyrazole derivatives of formula (I): wherein R' is hydrogen or methyl; Ar is pyridyl, thienyl, or optionally substituted phenyl; X is NH2, H, OH, halogen or C1-3 alkyl; and R is OH, OM, O-alk, NH2, NH-alk, N(alk)2 or N-alken-N-(alk)2; wherein alk is C1-5 alkyl; alken is (CH2)2 or (CH2)3 and M is a non-toxic cation; are useful in lowering blood urate levels in mammals.

  式 (I) 的吡唑衍生物： 其中 R' 是氢或甲基；Ar 是吡啶基、噻吩基或任选取代的苯基；X 是 NH2、H、OH、卤素或 C1-3 烷基；R 是 OH、OM、O-alk、NH2、NH-alk、N(alk)2 或 N-烯-N-(alk)2；其中烷是 C1-5 烷基；烯是 (CH2)2 或 (CH2)3，M 是无毒阳离子。
• Pyrazole derivatives as inhibitors of arachidonic acid-induced platelet aggregation
  作者：Serkan Levent、Burcu Çalışkan、Murat Çiftçi、Yeşim Özkan、İdil Yenicesu、Hüseyin Ünver、Erden Banoglu

  DOI：10.1016/j.ejmech.2013.03.048

  日期：2013.6

  Antiplatelet drugs are promising therapeutics to intervene with platelet aggregation in arterial thrombosis, most prominently in myocardial infarction and ischemic stroke. Here, we describe the synthesis and structure activity relationships of potent inhibitors of platelet aggregation based on the 1,5-diarylpyrazol-3-carboxamide scaffold. Analogs from this series demonstrated potent anti-aggregatmy activities against arachidonic acid-induced platelet aggregation, as measured by turbidimetric method of Born. 1,5-Diarylpyrazole-3-carboxamides obtained with small-basic amines (7, 8, 50, 51, 61, 62) displayed the strongest activity with IC50 values in low nanomolar range (5.7-83 nM). On the basis of their high potency in cellular environment, these straightforward pyrazole derivatives may possess potential in the design of more potent compounds for intervention with cardiovascular diseases. (C) 2013 Elsevier Masson SAS. All rights reserved.
• A Potent and Highly Efficacious Bcl-2/Bcl-xL Inhibitor
  作者：Angelo Aguilar、Haibin Zhou、Jianfang Chen、Liu Liu、Longchuan Bai、Donna McEachern、Chao-Yie Yang、Jennifer Meagher、Jeanne Stuckey、Shaomeng Wang

  DOI：10.1021/jm4001105

  日期：2013.4.11

  Our previously reported Bcl-2/Bcl-xL inhibitor, 4, effectively inhibited tumor growth but failed to achieve complete regression in vivo. We have now performed extensive modifications on its pyrrole core structure, which has culminated in the discovery of 32 (BM-1074). Compound 32 binds to Bcl-2 and Bcl-xL proteins with K-i values of <1 nM and inhibits cancer cell growth with IC50 values of 1-2 nM in four small-cell lung cancer cell lines sensitive to potent and specific Bcl-2/Bcl-xL inhibitors. Compound 32 is capable of achieving rapid, complete, and durable tumor regression in vivo at a well-tolerated dose schedule. Compound 32 is the most potent and efficacious Bcl-2/Bcl-xL inhibitor reported to date.